Banfi Cristina, Baetta Roberta, Gianazza Erica, Tremoli Elena
Centro Cardiologico Monzino, IRCCS, Milano, Italy.
Centro Cardiologico Monzino, IRCCS, Milano, Italy.
Drug Discov Today. 2017 Jun;22(6):848-869. doi: 10.1016/j.drudis.2017.03.001. Epub 2017 Mar 8.
Proteomic-based techniques provide a powerful tool for identifying the full spectrum of protein targets of a drug, elucidating its mechanism(s) of action, and identifying biomarkers of its efficacy and safety. Herein, we outline the technological advancements in the field, and illustrate the contribution of proteomics to the definition of the pharmacological profile of statins, which represent the cornerstone of the prevention and treatment of cardiovascular diseases (CVDs). Statins act by inhibiting 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase, thus reducing cholesterol biosynthesis and consequently enhancing the clearance of low-density lipoproteins from the blood; however, HMG-CoA reductase inhibition can result in a multitude of additional effects beyond lipid lowering, known as 'pleiotropic effects'. The case of statins highlights the unique contribution of proteomics to the target profiling of a drug molecule.
基于蛋白质组学的技术为识别药物的全谱蛋白质靶点、阐明其作用机制以及鉴定其疗效和安全性的生物标志物提供了强大工具。在此，我们概述该领域的技术进展，并举例说明蛋白质组学对他汀类药物药理学特征定义的贡献，他汀类药物是预防和治疗心血管疾病（CVD）的基石。他汀类药物通过抑制3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶发挥作用，从而减少胆固醇生物合成，并因此增强血液中低密度脂蛋白的清除；然而，HMG-CoA还原酶抑制除了降低血脂外还可导致多种其他效应，即所谓的“多效性效应”。他汀类药物的案例凸显了蛋白质组学对药物分子靶点分析的独特贡献。
